Aims Midazolam is given intravenously for induction of anaesthesia and conscious sedation and by subcutaneous infusion in patients in palliative care units. The objective of the present study was to determine the absolute bioavailability of subcutaneous midazolam and its pharmacokinetics in young, healthy, male volunteers. Methods Eighteen volunteers were given single doses of 0.1 mg kg − 1 midazolam i.v. and s.c. after a wash-out period of 7-15 days in an open-label, randomized, crossover study. Blood samples were collected up to 12 h post-infusion. Plasma concentrations of midazolam and of its two metabolites, 1 ′ -OHM and 4-OHM, were assessed using an h.p.l.c.-MS method (LOQ 0.5 ng ml − 1 for each analyte). Vital signs, cardiac parameters and oximetry were monitored. Local tolerance was determined and adverse events were also monitored. Results After s.c. infusion t max and C max were 0.51 ± 0.18 h and 127.8 ± 29.3 ng ml − 1 (mean ± s.d.), respectively. No statistically significant difference was detected in AUC(0, ∞ ) after i.v. and s.c. administration. The mean ( ± s.d.) absolute bioavailability of subcutaneous midazolam was 0.96 ( ± 0.14) (CI 0.84, 1.03). Mean ( ± s.d.) t 1 /2 was similar after s.c. (3.2 ( ± 1.0) h) and i.v. infusion (2.9 ( ± 0.7) h), although a statistically significant difference was reached ( P < 0.05). Mean CL and V of i.v. midazolam were 4.4 ± 1.0 ml min − 1 kg − 1 and 1.1 ± 0.2 l kg − 1 (mean ± s.d.), respectively. Plasma concentrations of 1'-OHM were higher than those of 4-OHM. Few mild and transient adverse events were noted and there were no clinically significant effects on EEG, blood pressure and laboratory parameters. Conclusions This study has shown that subcutaneous midazolam has excellent bioavailability and that administration of midazolam by this route could be preferable when the intravenous route is inappropriate.
The purpose of this paper is to describe the impact of exposure to influenza on hospitalizations and deaths in the elderly residents of long-term care facilities (LTCFs). An observational, longitudinal, prospective, multicenter, cohort study collected influenza and influenza-like cases, diseases, hospitalizations, and deaths of dependent elderly residents of French LTCFs during the 2004-2005 seasonal influenza epidemic. A total of 8,041 residents of 98 participating LTCFs were included. The mean age was 85 +/- 9 years; 93% were vaccinated against influenza and 64% of the residents were exposed to influenza during the epidemic. Exposure to influenza increased both the all-cause risk of hospitalization (9.2% of the residents exposed vs. 7.4% of the residents not exposed) (relative risk, RR [95% confidence interval, CI] = 1.24 [1.05; 1.47]) and the all-cause risk of death (5.8% vs. 4.3%) (RR [95% CI] = 1.36 [1.10; 1.70]). Exposure to influenza increased the risks of death and hospitalization. Additional measures should be taken to avoid influenza exposure and apply recommendations more thoroughly in the particularly susceptible population of elderly LTCF residents.
The pharmacokinetics and tissue penetration of ceftiaxone after a single intravenous injection of 1,000 mg to 17 patients for antibiotic prophylaxis in thoracic surgery were studied. The patients were scheduled for elective noncardiac thoracic surgery. Adequate levels in serum (higher than Noncardiac thoracic surgery is "contaminated-aseptic surgery" in most cases (4,6,7,11). Antibiotic prophylaxis is used against pathogens most likely to contaminate the surgical wound: Escherichia coli, various members of the family Enterobacteriaceae, Streptococcus spp., Haemophilus influenzae, Staphylococcus aureus, and Pseudomonas spp. (4,6,7,11 Ceftriaxone concentrations were determined by high-performance liquid chromatography (HPLC) (19), with a normal-phase technique and an NH-bonded-phase column (Spherisorb C18 Waters; 100 mm; 5-pm internal diameter).The mobile phase was a combination of acetonitrile (50 ml)
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